CN110433230A

CN110433230A - The therapeutical uses of Chardonnay seed products

Info

Publication number: CN110433230A
Application number: CN201910426268.4A
Authority: CN
Inventors: 托里·詹姆斯·阿尔维克; 丽贝卡·苏珊·利普森; 华莱士·H·约科亚马
Original assignee: US Department of Agriculture USDA; Sonomaceuticals LLC
Current assignee: US Department of Agriculture USDA; Sonomaceuticals LLC
Priority date: 2012-04-30
Filing date: 2013-04-29
Publication date: 2019-11-12
Also published as: CN104519895B; US20190269748A1; US20240024404A1; EA201491817A1; US11723943B2; US20150132419A1; EP2844266A2; US10772924B2; KR20150018784A; KR102149348B1; CA2871265A1; JP2015523321A; WO2013165921A3; BR112014026926A2; BR112014026926B1; IN2014DN09085A; AU2013256577B2; US10105409B2; JP6562837B2; US20210236579A1

Abstract

This disclosure relates to the health benefits of Chardonnay seed products.

Description

The therapeutical uses of Chardonnay seed products

The application is that the China of entitled " therapeutical uses of Chardonnay seed products " that the applying date is on April 29th, 2013 is special The divisional application of sharp application number 201380026061.9.

1. background technique

1.1Metabolic disorder

It is (non-that obesity is well known as many very common diseases such as atherosclerosis, hypertension, 2 patients with type Ⅰ DM Insulin-dependent diabetes mellitus (NIDDM)), dyslipidemia, coronary heart disease and osteoarthritis and various malignant progressions Risk factor.It also causes considerable problem by reducing motility and reducing quality of life.Obesity and thus there are also this The disease incidence of a little diseases is increasing in entire industrialised world.

Term obesity refers to that adipose tissue is excessive.Obesity is preferably regarded as being to confer to health risk in this context Any degree crosses fattiness.Normally the line of demarcation between obese individuals may be only approximate, but be assigned by obesity The health risk given may be fat increased continuity.

It will increase premature death and illness such as diabetes, dyslipidemia, hypertension, artery congee Mild Obesity disease The risk of sample sclerosis, gallbladder disease and certain form of cancer.In the western industrial world, the illness rate of obesity was in the past Decades in dramatically increase.Due to the high incidence and its health consequences of obesity, prevention and treatment should be one and answer The public health problem that high-priority considers.

When Energy intaking is more than expenditure, waste heat major storage is in adipose tissue, and if this just putting down only Weighing apparatus extends, then will lead to obesity, that is, and there are two the component parts of weight balance, and to any one side (intake or expenditure) It is abnormal all to may cause obesity.This process can be by increasing energy consumption (such as movement) or reducing Energy intaking (example Such as, diet) it is offset.In addition to movement, diet and food limitation, this be to vast subject it is infeasible, do not have also at present The compellent treatment of effective and acceptable losing weight.

A kind of possible mode for increasing energy consumption is to increase metabolic rate (metabolic rate).Therefore, pass through increase Metabolic rate and the drug to work are likely to be suited for treatment obesity, and are also applied for treatment Other diseases such as Atherosclerosis Change disease, hypertension, diabetes especially diabetes B (NIDDM (Non-Insulin Dependent Diabetes Mellitus)), dyslipidemia, hat Heart trouble, gallbladder disease, osteoarthritis and different types of cancer such as carcinoma of endometrium, breast cancer, prostate cancer and colon cancer and mistake Early dead risk.

Thus, identify that the reagent that can increase energy consumption will be desirable.It is preferred that this reagent can be day Right reagent and avoid side effect relevant to medical compounds.

1.2.Enteron aisle biocoene

The enteron aisle of baby is being sterile before birth.After birth, group is built by environmental bacteria rapidly in enteron aisle and is settled down until building Stand intensive enteron aisle biocoene.It is thin that the baby of vaginal delivery from its mother's vagina and faecal microbiota obtains intestinal flora cluster Bacterium.In contrast, by being not exposed to the vagina and faecal microbiota of its mother during the baby due of caesarean birth, and it is thus numerous The enteron aisle biocoene to spread out is different from the enteron aisle biological flora of vaginal delivery baby in composition.These enteron aisle biocoenes composition Difference after birth i.e. to be kept for the several months.Similarly, in breast-feeding and those formulations (formula milk, formula) The difference of enteron aisle biocoene composition is had been observed that between fed infant.

Adult's enteron aisle has about 10¹³(10,000,000,000,000) different settler (Backhead, F., et are planted al.(2004)PNAS Volume 101；No 44pp.15718-15723), and traverse many human culture background constructings three The constant microorganism parting (Arumugam, M.et al. (2011) Nature Vol.473pp.174-180) of kind.Enteron aisle biology Group is influenced by plant base polyphenol in diet, and it is believed that the microbes be translated into human host can biology (Rastmanesh, R. (2011), the Chemico-Biol.Interact.Vol.189pp.1-8 utilized；Moco, S., F.J.Martin, and S.Rezzi. (2012) J.Proteome Res.Volume 11, pp. 4781-4790).Serve as one kind Organ, the enteron aisle biocoene are also responsible for the vitamin such as cholecalciferol (vitamin D of conversion and production key₂₅), biology Plain (biotin), riboflavin (vitamin B₂), pantothenate (pantothenate) (vitamin B₅), ascorbic acid (vitamin C), Thiamine (vitamin B₁) and folic acid (vitamin B₉)；Especially it has been found that three kinds of microorganism parting (bacteroids (Bacteroides), Ruminococcus (Ruminococcus) and melaninogenicus (Prevotella)) in two kinds of (bacteroids And melaninogenicus).Some polyphenols by Norman doctor Hollenberg, Harvard Medical School medicine professor with its from The right expression of body is vitamin.However, modern diet, especially western diet may promote comprising a large amount of processed food It is formed into enteron aisle biocoene, cannot convert or produce these enough or optimised quantity crucial vitamins.

Thus, it identifies " nutrition blank " caused by Traditional Processed Food consumption " can be filled up " and adjusts human intestine's life Object group and realize health improvement reagent be desirable.It is preferred that this reagent is natural agent and avoids and pharmaceutical compound The relevant side effect of object.

2. summary of the invention

The disclosure of invention is related to the health benefits of Chardonnay (chardonnay, Xue Dangli, Chardonnay) seed products.

In certain aspects, the disclosure of invention is related to a kind of effectively improving lipid-metabolism in mammal by giving Amount method of the Chardonnay seed products to improve lipid-metabolism in mammal.

In certain aspects, the disclosure of invention is related to a kind of effectively improving metabolic rate in mammal by giving Method of the Chardonnay seed products of the amount of (metabolic rate) to improve mammalian metabolism rate.

The disclosure of invention further relates to one kind and effectively treats or prevents fertilizer in mammal by giving to mammal The Chardonnay seed products of the amount of fat disease are to treat or prevent obesity in mammal, cardiovascular disease, dyslipidemia, exception The method of lipoproteinemia or metabolism obstacles of blood glucose disease.

The disclosure of invention effectively treats or prevents the lactation by giving to mammal further to one kind Method of the Chardonnay seed products of the amount of animal center angiosis to treat or prevent mammal angiosis.Certain In aspect, cardiovascular disease is arteriosclerosis, atherosclerosis, apoplexy, ischemic, endothelial dysfunction disease, peripheral blood vessel Disease, coronary heart disease, myocardial infarction, cerebral infarction or restenosis.

The disclosure of invention effectively treats or prevents the lactation by giving to mammal further to one kind Method of the Chardonnay seed products of the amount of dyslipidemia to treat or prevent dyslipidemia in mammal in animal.In In some aspects, the dyslipidemia is high-density lipoprotein (HDL) cholesterol of hyperlipemia or low blood level.In certain sides In face, the hyperlipemia is familial hypercholesterolemia, familial mixing hyperlipemia, reduction or shortage property lipoprotein lipid Enzyme level or activity, hypertriglyceridemia, hypercholesterolemia, high blood level ketoboidies, high blood level Lp (a) cholesterol, height Blood level low-density lipoprotein (LDL) cholesterol, high blood level very low density lipoprotein (VLDL) cholesterol or high blood level are non-ester Change fatty acid.

The disclosure of invention effectively treats or prevents the dyslipoproteinemia by giving further to one kind Amount Chardonnay seed products treat or prevent mammal in dyslipoproteinemia method.In certain aspects, institute Stating dyslipoproteinemia is high blood level LDL, high blood level apolipoprotein B (apo B), high blood level Lp (a), high blood level Apo (a), high blood level VLDL, low blood level HDL, reduction or shortage property lipoprotein lipase levels or activity, low alpha lipoprotein blood Disease, lipoprotein abnormalities relevant to diabetes, with obesity-related lipoprotein abnormalities, rouge egg relevant with alzheimer's disease Bai Yichang or familial mix hyperlipemia.

The disclosure of invention effectively treats or prevents mammal by giving to mammal further to one kind Method of the Chardonnay seed products of the amount of middle metabolism obstacles of blood glucose disease to treat or prevent metabolism obstacles of blood glucose disease in mammal.In In some aspects, the metabolism obstacles of blood glucose disease is impaired glucose tolerance, insulin resistance (insulin resistance), pancreas islet Plain tolerance correlation breast cancer, colon cancer or prostate cancer, diabetes, pancreatitis, hypertension, polycystic ovary disease, high-level blood pancreas Island element or high-level blood glucose.In certain aspects, the diabetes are Non-Insulin Dependent Diabetes Mellitus (NIDDM), pancreas islet Plain dependent diabetes (IDDM), gestational diabetes (GDM) or maturity onset diabetes of the young (MODY, maturity onset diabetes of the young)。

The disclosure of invention effectively treats or prevents mammal by giving to mammal further to one kind Method of the Chardonnay seed products of the amount of middle metabolic syndrome to treat or prevent metabolic syndrome in mammal.

In certain aspects, the amount given effectively adjusts one or more participation fat, cholesterol and/or Bile metabolism Gene expression.In a specific embodiment, the amount effectively improves the expression of ACOX1 in hepatic tissue, improves in hepatic tissue The expression of CYP51 improves the expression of CYP7al in hepatic tissue, reduces the expression of SCD1 in hepatic tissue, and/or reduce in hepatic tissue The expression of ABCG5, for example, at least 10%, at least 20%, at least 50% or at least 100%.

The disclosure of invention effectively improves the mammal intestine by giving to mammal further to one kind The Chardonnay seed products of the amount of clostridium (Clostridium) amount of bacteria in road are to improve Clostridial bacteria in mammalian gut The method of amount.

The disclosure of invention effectively improves the mammal intestine by giving to mammal further to one kind The Chardonnay seed products of the amount of enterobacteria (Enterobacteriaceae) amount of bacteria in road are to reduce mammalian gut The method of middle Enterobacteriaceae amount.

By giving to the mammal, to effectively improve the lactation dynamic further to one kind for the disclosure of invention The Chardonnay seed products of the amount of bacteroides fragilis (Bacteroides fragilis) group (group) amount of bacteria in object enteron aisle Method to improve bacteroides fragilis group amount of bacteria in mammalian gut.

The disclosure of invention effectively treats or prevents lactate acid by giving to mammal further to one kind Method of the Chardonnay seed products of the amount of poisoning to treat or prevent lactic acidosis in mammal.

In the certain embodiments of these methods, it is not the of Chardonnay seed products that Xiang Suoshu mammal, which is given, Two grape seeds or grape skin product.In certain aspects, Chardonnay seed products and the second grape seed or grape skin product The curative effect that provides of combination or health benefits be more than individually to give the effects of Chardonnay seed products.

In certain aspects, the Chardonnay seed products are by having at least 600mg epicatechin/100g seed table Catechin content or the preparation of the seed of at least 700mg epicatechin/100g seed epicatechin content.In specific embodiment In, the epicatechin content range is 600-800mg/100g seed or 650-800mg/100g seed.

In some embodiments, the Chardonnay seed products introduce food or beverage products.

In some embodiments, the Chardonnay seed products are Chardonnay seed meals.In some embodiments, institute Stating Chardonnay seed products is Chardonnay seed extract.In some embodiments, the Chardonnay seed products come spontaneous The grape being longer than in Winkler (Winkler) local climate I, II, III or IV type.

In some embodiments, the mammal is domestic pets, for example, cat or dog.In the other of these methods In embodiment, the mammal is the mankind.In other embodiments, the mankind are babies.

The disclosure of invention is further to a kind of infant formula product (infant comprising Chardonnay seed products Formula) and using the infant formula product promote the method for baby intestinal microbiologic population development.In certain aspects, The infant formula product promotes intestinal microbiota to develop when giving baby by adjusting the level of enteric bacteria (development).In some embodiments, the baby passes through cesarean section delivery.In some embodiments, the baby Youngster is that formulation is fed.

3. Detailed description of the invention

Fig. 1: Chardonnay (Chr), solution hundred patch up (Cabernet Sauvignon) (Cab) and hila (Syrah) (Syr) seed (Sd) and skin (Sk) albumen, fat, ash content, carbohydrate and total dietary fiber.

Fig. 2: the diet composition of hamster in embodiment 1.

Fig. 3: seed feeding weight of the animal in terms of week in embodiment 1.

Fig. 4: skin feeding weight of the animal in terms of week in embodiment 1.

Fig. 5: the food intake weekly of the animal of embodiment 1.

Fig. 6: the total food intake of the animal of embodiment 1.

Fig. 7: the total amount of heat intake of the animal of embodiment 1.

Fig. 8: plasma lipoprotein cholesterol levels of the animal of embodiment 1 at the end of surrounding.

Fig. 9: blood glucose level of the animal of embodiment 1 at the end of surrounding.

Figure 10: organ weight of the animal of embodiment 1 at the end of surrounding.

Figure 11: epicatechin is horizontal in the seed and skin of different grape varieties.

Figure 12: embodiment 2 includes the body of the animal of the feeding diet of 3wt%, 7wt% and 10wt% Chardonnay seed meal Weight, weight gain and total food intake.

Figure 13: 2 feeding Chardonnay seed ethanol extract (40EtChrSdEx) of embodiment, Chardonnay seed methanol extract Object (MeChrSdEx), Chardonnay seed ethyl alcohol extraction residue (40EtChrSdRes), Chardonnay seed methanolic extract are residual Excess (MeChrSdRes), 10%, 7% and 3% (respectively 10%ChrSd, 7%ChrSd and 3% according to diet weight ChrSd White Riesling (White Riesling) seed meal (10%WRSd) of Chardonnay seed meal, 10% diet weight) With the animal of Sauvignon Blanc (Sauvignon Blanc) seed meal (10%SBSd) of 10% diet weight at the end of surrounding VLDL, LDL and HDL cholesterol levels.

Figure 14: 2 feeding Chardonnay seed ethanol extract (40EtChrSdEx) of embodiment, Chardonnay seed methanol extract Object (MeChrSdEx), Chardonnay seed ethanol extract residue (40EtChrSdRes), Chardonnay seed methanolic extract Residue (MeChrSdRes), 10%, 7% and 3% diet weight (respectively 10%ChrSd, 7%ChrSd and 3%ChrSd) Chardonnay seed meal, White Riesling (White Riesling) seed meal (10%WRSd) and 10% of 10% diet weight LDL/HDL of the animal of Sauvignon Blanc (Sauvignon Blanc) seed meal (10%SBSd) of diet weight at the end of surrounding Cholesterol ratio.

Figure 15: 2 feeding Chardonnay seed ethanol extract (40EtChrSdEx) of embodiment, Chardonnay seed methanol extract Object (MeChrSdEx), Chardonnay seed ethanol extract residue (40EtChrSdRes), Chardonnay seed methanolic extract The diet weight of residue (MeChrSdRes), 10%, 7% and 3% (respectively 10%ChrSd, 7%ChrSd and 3%ChrSd) Chardonnay seed meal, White Riesling (White Riesling) seed meal (10%WRSd) and 10% of 10% diet weight Liver of the animal of Sauvignon Blanc (Sauvignon Blanc) seed meal (10%SBSd) of diet weight at the end of surrounding, epididymis Fatty (EA) and retroperitoneal fat (RA) weight.

Figure 16: the relatively fatty gene expression of embodiment 3.

Figure 17: the opposite liver gene expression of embodiment 3.

Figure 18: 4 feeding of embodiment supplement Chardonnay seed meal (CharSdFl),Grape seed extract (VC1 and VC7), MegaBP grape seed extract (BP1, BP7),Grape seed extracts Total plasma lipoprotein of the animal of the diet of object (L1, L7), catechin (Cat) and epicatechin (EpiCat) at the end of surrounding Cholesterol levels.

Figure 19: 4 feeding of embodiment supplement Chardonnay seed meal (CharSdFl),Grape seed extract (VC1 and VC7), MegaBP grape seed extract (BP1, BP7),Grape seed extracts The animal of the diet of object (L1, L7), catechin (Cat) and epicatechin (EpiCat) VLDL, LDL at the end of surrounding and HDL cholesterol levels.

Figure 20: 5 feeding control diet of embodiment, supplement solution hundred patch up the high fat diet of seed meal (RGF+HF), supplement rosy clouds Total fecal bacteria of the animal of the high fat diet and high-fat control diet (HF) of Dolly seed meal (WGF+HF) is horizontal.

Figure 21: 5 feeding control diet of embodiment, supplement solution hundred patch up the high fat diet of seed meal (RGF+HF), supplement rosy clouds The enterococcus spp of the animal of the high fat diet and high-fat control diet (HF) of Dolly seed meal (WGF+HF) (Enterococcus spp.) is horizontal.

Figure 22: 5 feeding control diet of embodiment, supplement solution hundred patch up the high fat diet of seed meal (RGF+HF), supplement rosy clouds The Bifidobacterium of the animal of the high fat diet and high-fat control diet (HF) of Dolly seed meal (WGF+HF) (Bifidobacterium spp.) is horizontal.

Figure 23: 5 feeding control diet of embodiment, supplement solution hundred patch up the high fat diet of seed meal (RGF+HF), supplement rosy clouds The Lactobacillus of the animal of the high fat diet and high-fat control diet (HF) of Dolly seed meal (WGF+HF) (Lactobacillus spp.) is horizontal.

Figure 24: 5 feeding control diet of embodiment, supplement solution hundred patch up the high fat diet of seed meal (RGF+HF), supplement rosy clouds IV groups of bacteria levels of clostridium of the animal of the high fat diet and high-fat control diet (HF) of Dolly seed meal (WGF+HF).

Figure 25: 5 feeding control diet of embodiment, supplement solution hundred patch up the high fat diet of seed meal (RGF+HF), supplement rosy clouds The bacteroides fragilis group (group) of the animal of the high fat diet and high-fat control diet (HF) of Dolly seed meal (WGF+HF) Bacteria levels.

Figure 26: 5 feeding control diet of embodiment, supplement solution hundred patch up the high fat diet of seed meal (RGF+HF), supplement rosy clouds The enterobacteria of the animal of the high fat diet and high-fat control diet (HF) of Dolly seed meal (WGF+HF) is horizontal.

4. specific embodiment

4.1.Chardonnay seed products

Obesity and other diseases are treated or prevented the present invention relates to Chardonnay seed products and using Chardonnay seed products The method of disease.It is preferred that the Chardonnay seed products are raw by the grape for being grown on Winkler (Winkler) local climate I-IV type It produces (Jones et al, 2010, Am.J.Enol.Vitic.61 (3): 313-326).In some embodiments, the rosy clouds are more Beautiful seed products are by being grown on north plus the coastal mountain valley Li Fuliya, for example, receiving the pa mountain valley (Napa) and/or Suo Nuoma (Sonoma) The grape in mountain valley produces.In another embodiment, the Chardonnay seed products are by being grown on other hotter inland mountain valleys Vineyard, for example, the grape of Winkler (Winkler) local climate IV-V type produces.In a preferred embodiment, described Chardonnay seed products are from the grape being grown in coastal area.

In one embodiment, the Chardonnay seed products contain the non-fat portion of Chardonnay seed, such as Chardonnay Pomace coarse powder (grits, meal), Chardonnay pomace powder (fine powder, flour), Chardonnay seed meal, or most preferably, Chardonnay Seed meal (fine powder, fine grinding powder, flour).In some embodiments, the Chardonnay seed products include to pass through organic solvent It is not extractible, for example, passing through ethyl alcohol and/or the content (content) of the not extractible degreasing Chardonnay seed of methanol.In In some aspects, the Chardonnay seed products are by epicatechin content at least 600mg epicatechin/100g seed or table catechu The preparation of cellulose content at least 700mg epicatechin/100g seed seed.In a specific embodiment, the epicatechin content Range is 600-800mg/100g seed or 650-800mg/100g seed.

As utilized herein, " Chardonnay seed meal " is ground entire seed and " Chardonnay seed meal (Chardonnay Seed fine powder) " it is grinding seed after extract oil.Chardonnay seed meal can be used known in the art from seed extract oil It generates " cold pressing ", " hot pressing " or the solvent extraction process of defatted seed powder and obtains.Coarse powder or powder can be by using suitable The conventional drying technique of dried foods product is dried until moisture content needed for (acquisition).

The coarse powder or powder of the drying further grind under ambient temperature conditions and are formed with free-flowing particle Chardonnay seed powder.In one embodiment, the particle that flows freely can be the size no more than 841 μm (20 mesh) To the size for being no more than 37 μm (400 mesh).In some embodiments, the size be no more than 20 mesh, 40 mesh, 60 mesh, 80 mesh, 100 mesh, 200 mesh, 300 mesh or 400 mesh.

In a kind of illustrative methods, Chardonnay seed meal is by separation and dry shrimps and crabs seed, for example, by rosy clouds The squeezing of Dolly grape is made at the pomace generated after grape juice (for example, grape wine is made).The grape seed can " cold press " and by its degreasing (Chardonnay seed oil of the production as byproduct).Grape seed powder is carried out by the press cake after oil extraction Grinding.In an embodiment, the seed is separated from Grape Skin after grape extraction juice, through over cleaning, mechanical degreasing, Fine gtinding and the flowable powder for sieving and generating 100 mesh (150 μm).

Chardonnay seed meal also can be from Apres Vin (Yakima, Washington), Botanical Oil Innovations (Spooner, the state of Wisconsin) or Fruitsmart, Inc. (Grandview, Washington) are commercially available.It is described FruitSmart Chardonnay seed meal is the flowable powder of 85 mesh, but further can grind and sieve and generate with smaller The powder of particle size.

In one embodiment, skin, stem and leaf (rest part of pomace) are removed from seed before squeezing.It removes Skin, stem and leaf allow to carry out optimal oil expression.

" Chardonnay seed extract " passes through solvent extraction Chardonnay seed such as ethyl alcohol or methanol using suitable solvent And it is made.For example, " 40EtChrSdEx " is that 40% ethanol solution is used to extract as Chardonnay seed made of Extraction solvent Object.The extracting method can also generate the residual of insoluble solid other than the extract containing the Solvent soluble components Excess.

4.2.Effective quantity

In the embodiment of the method for the invention, percentage specific consumption of the Chardonnay seed meal as day diet Amount is at least 3%, at least 5% or at least 8% in mass.It is preferred that 5%-10%, more preferable 7%, and in some embodiments In 10% day diet in mass be Chardonnay seed meal.

In the embodiment of the method for the invention, percentage specific consumption of the Chardonnay seed meal as day diet The heat (calorie) for the wastage in bulk or weight that amount is at least 3%, at least 5%, or at least 8%.It is preferred that 5%-10%, more preferable 7%, and The 10% day heat comes from Chardonnay seed meal in some embodiments.

In another embodiment, the amount of the Chardonnay seed meal of daily consumption is at least 10g, at least 15g, at least 20g, At least 25g, at least 30g, at least 35g, at least 40g, or at least 45g.It is preferred that every daily consumption 50g Chardonnay seed meal.

In another embodiment, the amount of the Chardonnay seed meal of every daily consumption is at least 1 soupspoon, at least 2 soupspoons, at least 3 soupspoons, at least 4 soupspoons, or at least 5 soupspoons.

In another embodiment, the amount of the Chardonnay seed meal of daily consumption is based on Chardonnay seed meal weight: weight is At least 0.2g/kg, at least 0.5g/kg, or at least 0.7g/kg.It is preferred that consuming at least 1g Chardonnay seed meal/kg weight daily.

In certain aspects, the amount for giving Chardonnay seed meal effectively adjusts one or more participations fat, cholesterol, And/or the expression of the gene of Bile metabolism.In a specific embodiment, the amount effectively improves the expression of ACOX1 in hepatic tissue, The expression of CYP51 in hepatic tissue is improved, the expression of CYP7al in hepatic tissue is improved, reduces the expression of SCD1 in hepatic tissue, and/or The expression of ABCG5 in hepatic tissue is reduced, for example, at least 10%, at least 20%, at least 50%, or at least 100%.

Chardonnay seed meal can be extracted with Chardonnay pomace coarse powder, pomace powder, Pi Fen, seed in the method for the invention Object or seed meal replace.Chardonnay pomace coarse powder, pomace powder, Pi Fen, seed extract or the consumption of seed meal daily requirement And the amount for reaching specified rate Chardonnay seed meal same benefits can be readily determined by those skilled in the art in the art.Example Such as, it is contemplated that needs are consumed the identical benefit that about three times Chardonnay skin powder can be only achieved the Chardonnay seed meal of specified rate by subject Place.

In some embodiments, the Chardonnay seed products, for example, Chardonnay seed meal, takes at least one week two It is secondary, at least three times a week, or once every other day.It is preferred that the Chardonnay seed products are introduced into the day diet.

The Chardonnay seed products, for example, the time quantum that Chardonnay seed meal is taken be enough to treat and/or prevent it is suitable From the illness for the treatment of and/or prevention in Chardonnay seed products as described herein.The Chardonnay seed products can take With at least one week, at least 2 weeks, at least 3 weeks, at least one moon, at least two moon, at least three moon, at least six moon, at least a year, Or indefinite duration (indefinitely) takes.

In the certain embodiments of these methods, it is not the second of Chardonnay seed products that Xiang Suoshu mammal, which is given, Grape seed or grape skin product.In certain aspects, Chardonnay seed products and the second grape seed or grape skin product The curative effect provided is provided or health benefits have been more than individually to give the effect of Chardonnay seed products.

In other embodiments, the amount of Chardonnay seed products and the amount of the second grape seed or grape skin product are through selecting It selects and to be allowed to effect obtained at least identical as by individually giving the Chardonnay seed products effect achieved of specified rate.

4.3.Chardonnay seed composition

The Chardonnay seed products can be contained in various food products, if nutritious drink is (for example, nutrition milk shake (nutritional shakes)), bakery (for example, small biscuit, Brownie, cake, bread, biscuit, crispbread), cloth Fourth, candy (e.g., preserved fruit), snack food (for example, muffin), ice cream, parfait and novelty (novelties) or non- Bake ertruding food product product such as stick, including health or energy stick.The Chardonnay seed products can be used as nutritional supplement, Or it provides in form of tablets or as the powder for being suitable as nutraceutical additive.

In one embodiment, the Chardonnay seed products can be blended with other dry food materials and are used to prepare Food product rich in Chardonnay seed products.Dry food material includes, for example, dry starch-containing material, dry material containing albumen Material or combinations thereof.Suitable starch-containing material can be derived from, for example, rice, corn, soybean, sunflower, rape (rape, Canola), wheat, oat, rye, potato, or any combination thereof.It is suitably dry to be may originate from containing protein material for example, meat, Milk, fish or any combination thereof.It is applied for baking, the Chardonnay seed products are suitble to the amount ranges used to be 3%~5% Dry food material (for example, white or wholemeal).The dry food can also optionally include other ingredient such as vitamin, Mineral-supplemented dose, salt, colorant, flavoring agent, flavoring agent or sweetener.

Chardonnay seed products can be introduced into beverage, processing meat product, frozen dessert, confectionary products, dairy-type product, sauce In composition and bread basket.Beverage products include, for example, Sorbet (smoothies), infant formula product, fruit drink, Boruga, coffee beverage, beer, dry beverage mixture, tea merge beverage (tea fusion beverages), movement drink Material, soy sauce (soy liquor), carbonated drink, sludge ice (slushes) and frozen drink mixes.Meat products include, for example, grinding Chicken meat product, adds extreme misery leg product, boulogna sausage, hot dog, Frank (franks), chicken patties, chicken nugget (chicken nugget), Minced beef cutlet, fish cake, minced fillet, bacon, pork luncheon meat, sandwich fillings, cooked meat product (deli meat), jerky based food, meat Ball, jerky (jerky), beef item (fajitas), Baconic's piece (bacon bits) inject meat and German-style sausage.Confectionary products Including, for example, chocolate, mousse, chocolate coating, Yoghourt coating, cocoa power, frosting (frosting), toffee, energy stick and Loaf sugar (candy bar).Frozen dessert class product includes, for example, ice cream, maltose (malt), milk shake (shakes), ice Rod, ice cream and freezing pudding product.Dairy-type product includes, for example, Yoghourt, cheese, ice cream spray cream (whipped Topping), coffee cream, cream cheese, Yoghourt, white spirit junket (cottage cheese), butter, mayonnaise (mayonnaise), milk base sauce, newborn base mayonnaise and cheese curd.Bread basket includes, for example, bread, muffin, hundred Lucky cake, noodles, biscuit, thin pancake, Waffle, rusk, semolina, French fries, corn-dodger, cake, crispbread are early It eats cereal (including instant and cooked cereal), pretzels, rusk mixture, melbatoast, stick bread, frying Bread, fillings, energy stick, baked donut, cake, puffed rice, maize roll, fried covering layer, batter wrap up in powder, crisp skin, chocolate cake Cake, pie, extruding soya-bean cake can beautiful cake, croissant, powder and maize gruel.Sauce composition includes mayonnaise, and nut butter is smeared Sauce (for example, peanut butter spread), thick gravy, sauce, salsa this, jam, cheese spread, mayonnaise, sauce, fermented bean curd, Dip in sauce, fruit sugar syrups and maple syrup (maple syrup).Sauce composition can also include that auxiliary maintains the outstanding of composition homogeneity Floating auxiliary agent (suspending agent).The example of suitable suspension aids includes polysaccharide, such as starch, cellulose (for example, microcrystalline cellulose) and Carrageenan and polyuronide, such as pectin.Gelatin is another suspension aids example, it can also be used for beverage composition for treating dental erosion.Root The example of the additional supplement product prepared according to the present invention using pre-composition includes bean curd, prepares soybean essence, and powdered protein is mended Fill agent, fruit juice can mixed protein replenishers, foaming agent, clouding agent (clouding agent), baby food, vegetarian diet ball, meat Like object, egg product (for example, scrambled eggs), soup, chowder (chowder), meat soup, milk substitute, soya milk product, capsicum, fragrance is mixed Object is closed, sugar is spilt, fermented soya bean (soy whiz), salad topping, edible film, edible bar, chewing gum, Baconic's piece, vegetables volume, Piza Cake skin barrier layer (pizza crust barriers), soybean pie, no gas synthesize bean curd, bean product helper (soy Helper), soybean cotton candy (soy cotton candy), fruit fourth, pizza roll, mashed potatoes spin soybean fiber, beans Volume squeezes out snack (extruded snack), flavouring, lotion, fry (fries), gelatin dessert product, and vitamin is mended Fill agent, nutrition bar, dry cake, bread or muffin mix and can microwave wink dry mixture (microwavable instant dry mixes)。

In In a specific aspect, the Chardonnay seed products can be used as energy stick (be suitble to physiological activity consumption) or Generation meal stick.The energy stick can also contain one or more of vitamin, minerals, food supplement, plant for meal stick Product (botanical) or plant or herb extract or known in the art or energy stick or for meal stick used at Point, such as fruit juice or extract, herbal medicine (herb) or odoriferous herbs (herb flavor), natural or artificial flavors, vitamin, mine Substance, the extract containing antioxidant, ubiquinone, omega-fatty acid, Guarana, caffeine, theobromine, maltodextrin and Albumen.In some embodiments, the energy stick or for meal stick can have respectively 40/30/30 carbohydrate/egg Total utilisable energy of white/fat is horizontal.

The energy and the raising for locomitivity can be further supplemented for meal stick, mental capacity or cognition emphasis are strong Change and/or nutritional benefits.Exemplary replenishers include, but are not limited to vinpocetine, pervone ginkgo leaf essence (Vincamine Ginkgo Biloba), L-arginine, acetyl-L-carnitine, feverfen (Feverfew), DMAE (dimethylaminoethanol), DMAE Biatrate, acetic acid parachlorophenol ester, vitamin B complexing agent, ginseng, 5HTP (5-hydroxyryptophan), L-thiamine, androstene two Ketone, L-Glutamine, l-tyrosine, L- glycine；L-lysine；Lactalbumin；DHEA (dehydroepiandros-sterone).

In another aspect, the Chardonnay seed products can be provided in or be added to liquid or powder infant formula In product.The infant formula product can contain protein sources, fat source and/or carbohydrate source.The protein sources can It is, for example, dry or liquid milk, whey and/or casein or soybean protein.The fat source can be, for example, dairy products Fatty and/or one or more vegetable oil.The carbohydrate source can be, for example, lactose, glucose or sucrose.It is described In addition infant formula product can contain one or more vitamins and/or one or more minerals.In an embodiment In, the Chardonnay seed products can be added in commercially available liquid or powder infant formula product.

The Chardonnay seed composition also can containing one measure be not Chardonnay seed products the second grape kind Son or grape skin product.In some embodiments, the Chardonnay seed products of an amount are in the Chardonnay seed group Close the second grape seed and Grape Skin products substitution measured in object with one.It needs to be added in the Chardonnay seed composition It can be held very much with acquisition and the second grape seed of Chardonnay seed products same benefits or the amount of grape skin product of specified rate It changes places and is determined by those skilled in the art.

4.4.The therapeutical uses of Chardonnay seed compound powder

According to the present invention, composition of the invention includes Chardonnay seed compound powder, to subject, preferably to the mankind Subject gives, and lipid-metabolism increase is useful or desired in the subject.The subject may need Treatment or prevention cardiovascular disease, dyslipidemia, impaired glucose metabolism, Alzheimer's disease, X syndrome, PPAR are related Disfunction, septicemia, thrombus sexual disfunction (thrombotic disorder), obesity, pancreatitis, hypertension, kidney Disease, cancer, inflammation or impotence.

In another aspect of the present invention, composition of the invention includes Chardonnay seed compound powder, to tested Person preferably gives to human experimenter, and the biocenological adjusting of the enteron aisle described in the subject is useful or expectation 's.In one embodiment, the subject may need to treat or prevent, for example, lactic acidosis, colitis, or Colorectal cancer.In one embodiment, the subject is that heredity is susceptible to suffer from colon cancer.

In one embodiment, " treatment ", which refers to, improves a kind of disease or illness or its at least one recognizable disease Shape.In another embodiment, " treatment " refers to that improving at least one might not be joined by the recognizable measurable physiology of main body Number.In another embodiment, " treatment " refers to the progress for inhibiting disease or illness, either physically, for example, can distinguish The stabilization of symptom, physiologically, for example, the stabilization of physiological parameter, or both have both at the same time.In an embodiment also In, " treatment " refers to the breaking-out for delaying disease or illness.

In some embodiments, composition of the invention gives subject, the preferably mankind, as to the pre- of these diseases Anti- property measure.As utilized herein, " prevention " or " preventing ", which refers to, reduces the risk for obtaining given disease or illness.It is excellent at one In the aspect of choosing, the present composition gives subject as precautionary measures, and preferably to cardiovascular disease, dyslipidemia is different Normal lipoproteinemia, impaired glucose metabolism disease, Alzheimer's disease, X syndrome, the related dysfunction disease of PPAR are lost Mass formed by blood stasis, thrombus sexual disfunction, obesity, pancreatitis, hypertension, nephrosis, cancer, inflammation or impotence have inheritance susceptible The mankind of property.The example of this genetic predisposition includes but is not limited to the E4 allele of apo E, will increase alzheimer ' A possibility that silent disease；Afunction or null mutation are (for example, causing to replace in lipoprotein lipase gene coding region or promoter For the mutation in the code area of D9N and N291S；Review will increase cardiovascular disease, dyslipidemia and dyslipoproteinemia wind Gene mutation in the lipoprotein lipase gene of danger, referring to Hayden and Ma, 1992, Mol.Cell Biochem.113: 171-176)；Hyperlipemia and familial hypercholesterolemia are mixed with familial.

In another preference pattern of the embodiment, composition of the invention as precautionary measures give have pair Cardiovascular disease, dyslipidemia, dyslipoproteinemia, glucose metabolism disorders, Alzheimer's disease, X syndrome, PPAR Related dysfunction disease, septicemia, thrombus sexual disfunction, obesity, pancreatitis, hypertension, nephrosis, cancer, inflammation Or the subject of the non-genetic predisposition of impotence.The example of this non-genetic predisposition includes but is not limited to: bypass surgery With percutaneous transluminal coronary angioplasty (percutaneous transluminal coronary angioplasty), this is past It is past to will lead to restenosis, the acceleration form of atherosclerosis；Diabetes in women, this frequently can lead to polycystic ovary Disease；And cardiovascular disease, this frequently can lead to impotence.

In some embodiments, the mammal consumes high fat diet.In one embodiment, high-fat drink Food is that wherein at least 30%, 35% or 40% total day heat is obtained from the diet of fat.

In some embodiments, the second grape seed or grape skin product of non-Chardonnay seed meal are dynamic to the lactation It is more than the effect for individually giving Chardonnay seed meal effect that object, which is given and provided,.

4.4.1.Dyslipidemia

The present invention provides the methods for treating or preventing dyslipidemia, including give therapeutically effective amount to subject Chardonnay seed compound powder.

The term as used herein " dyslipidemia " refers to the disfunction for leading to or showing the circulation lipid of abnormal level.Blood Lipid level is excessively high to a certain extent in liquid, and composition of the invention gives subject and restores normal level.Lipid it is normal Level report is in medicine treatise well known by persons skilled in the art.For example, LDL, HDL, three ester of dissociative glycerin and other and rouge The recommendation blood level that matter is metabolized relevant parameter can be ground in the website of American Heart Association and national heart, lung and blood Study carefully the website of National Cholesterol Education Program find.Currently, the recommended levels of HDL cholesterol in blood are higher than 35mg/dL；The recommended levels of LDL cholesterol in blood are lower than 130mg/dL；The LDL:HDL cholesterol ratio recommended in blood Lower than 5:1, ideally 3.5:1；And the recommended levels of three ester of dissociative glycerin in blood are less than 200mg/dL.

The dyslipidemia that Chardonnay seed compound powder of the invention is suitable for treating or preventing includes but is not limited to height Blood lipid disease and low blood level high-density lipoprotein (HDL) cholesterol.In some embodiments, compound prevention through the invention Or the hyperlipemia for the treatment of is familial hypercholesterolemia；Familial mixes hyperlipemia；Reduction or shortage property lipoprotein lipid Enzyme level or activity, including the reduction or shortage caused by lipoprotein lipase mutations；Hypertriglyceridemia；Hypercholesteremia Disease；High blood level ketoboidies (such as β-OH butyric acid)；High blood level Lp (a) cholesterol；High blood level low-density lipoprotein (LDL) gallbladder is solid Alcohol；High blood level very low density lipoprotein (VLDL) cholesterol and high blood level non-esterified fatty acid.

Invention further provides lipid-metabolism in subject is changed, for example, reducing LDL in subject's blood, reduce In subject's blood dissociate triglycerides, increase subject's blood in HDL/LDL ratio, and inhibit saponification and/or Non-saponified fatty acid synthetic method, the method includes the rosy clouds for giving the amount for effectively changing lipid-metabolism to the subject are more Beautiful seed compound powder.

4.4.2.Cardiovascular disease

The present invention provides the methods for treating or preventing cardiovascular disease, including giving therapeutically effective amount to subject Chardonnay seed compound powder.The term as used herein " cardiovascular disease " refers to the disease of heart and the circulatory system.These diseases It is often related with dyslipoproteinemia and/or dyslipidemia.The present composition is suitable for the angiocarpy for preventing or treating Disease includes but is not limited to arteriosclerosis；Atherosclerosis；Apoplexy；Ischemic；Endothelial dysfunction disease, especially those shadows Ring the dysfunction of blood vessel elasticity；Peripheral artery disease；Coronary heart disease；Myocardial infarction；Cerebral infarction and restenosis.

4.4.3.Dyslipoproteinemia

The present invention provides the methods for treating or preventing dyslipoproteinemia, including give treatment to subject and have The Chardonnay seed compound powder of effect amount.

The term as used herein " dyslipoproteinemia " refers to the blood circulation lipoprotein for leading to or showing as abnormal level Disfunction.Lipoprotein levels are crossed up to a certain degree in blood, and composition of the invention gives subject and restores normal water It is flat.On the contrary, lipoprotein levels are crossed down to a certain degree in blood, composition of the invention gives subject and restores normal water It is flat.The normal level of lipoprotein is reported in medicine treatise known to those skilled in the art.

The dyslipoproteinemia that the present composition is suitable for preventing or treating includes but is not limited to high blood level LDL； High blood level apolipoprotein B (apo B)；High blood level Lp (a)；High blood level apo (a)；High blood level VLDL；Low blood level HDL；Reduction or shortage property lipoprotein lipase levels or activity, including the reduction or shortage caused by lipoprotein lipase mutations；Low α Lipoproteinemia；Lipoprotein abnormalities relevant to diabetes；With obesity-related lipoprotein abnormalities；With alzheimer's disease phase The lipoprotein abnormalities of pass；Hyperlipemia is mixed with familial.

The present invention also provides reducing, apo C-II in subject's blood is horizontal；Reduce subject's blood apo C-III water It is flat；Promoted HDL GAP-associated protein GAP level, including but not limited to apo A-I, apo A-I1, the apo A-IV of subject's blood and apo E；It improves the level of the apo E of subject's blood and promotes the method for removing triglycerides from subject's blood, it is described Method includes giving effectively to generate the reduction respectively to the subject, the Chardonnay seed compound powder for improving or promoting.

4.4.4.Metabolism obstacles of blood glucose disease

The present invention provides the methods for treating or preventing metabolism obstacles of blood glucose disease, including giving therapeutically effective amount to subject Chardonnay seed compound powder.The term as used herein " metabolism obstacles of blood glucose disease ", which refers to, leads to or shows as aberrant glucose storage And/or the illness utilized.Glucose metabolism mark (that is, blood insulin, blood glucose) is excessively high to a certain extent, composition of the invention It gives subject and restores normal level.On the contrary, the mark of glucose metabolism is crossed down to a certain degree, composition of the invention is given It gives subject and restores normal level.The normal mark of glucose metabolism is reported in medicine treatise well known by persons skilled in the art In.

The metabolism obstacles of blood glucose disease that the present composition is suitable for preventing or treating includes but is not limited to that impaired glucose is resistance to By property；Insulin resistance；The relevant breast cancer of insulin resistance, colon cancer or prostate cancer；Diabetes, including but not limited to Non-Insulin Dependent Diabetes Mellitus (NIDDM), insulin-dependent diabetes mellitus (IDDM), gestational diabetes (GDM) and youth Late-stage diabetic (MODY)；Pancreatitis；Hypertension；Polycystic ovary disease；With high-level blood insulin and/or hyperglycemia.

Invention further provides change subject in glycometabolism, for example, improve subject insulin sensitivity and/ Or the method for oxygen consumption, the method includes the Chardonnay seed meal combination for the amount for effectively changing glycometabolism is given to the subject Object.

4.4.5.The adjusting of enteric bacteria

People enteron aisle biocoene is divided into three quasi-microorganism partings according to the species of the bacterial community dominance.This is slightly Biological typing is bacteroid, Ruminococcus and melaninogenicus.It is found that the bacteroid microorganism parting can prepare several Vitamin, including C and H, and simultaneously it is found that the Prevost bacteria microorganism parting can prepare folic acid and vitamin B1.

The present invention provides the methods for adjusting enteric bacteria level, including give to subject and effectively adjust enteric bacteria water The Chardonnay seed compound powder of flat amount.As utilized herein, " it is horizontal to adjust enteric bacteria " and refers to (i) enteric bacteria level Total amount reduces, and/or the bacteria levels of (ii) total intestinal bacterial subpopulations (subset) increase or decrease.Total intestinal bacterial subpopulations It can be single species, belong to, section, mesh, guiding principle, door, or the combination of the above more than one.

For example, it is horizontal to adjust intestinal flora in the baby by caesarean deliveries, it may be possible to it is desirable, because described The bacteria planting of enteron aisle can postpone in the baby of caesarean birth compared to the baby of vaginal delivery.The difference of intestinal flora may be 6 months as long as (Grolund, M.et al, Journal of Pediatric are lasted up to after birth Gastroentero10gy&Nutrition, (1999), vol.28 (1): 19-25).For example, the baby by caesarean birth compares The bacterium of significant less bacteroides fragilis group can be colonized when the baby of vaginal delivery birth is in six-month-old.Seven days after birth, The baby of caesarean birth can have the higher levels of intestines as total enteric bacteria percentage compared to the baby that vaginal delivery is born Bacillus bacterium citric acid bacillus and Escherichia coli (Pandey, P.et al., J.Biosci. (2012) vol.37 (6): 989- 998).Chardonnay seed compound powder can be used in improving the level of bacteroides fragilis group bacterium and clostridium, and for example reduces and cut open Abdomen produces the level of enterobacteriaceae lactobacteriaceae in baby and promotes the biocenological formation of enteron aisle, closer to go out similar to vaginal delivery The intestinal microflora of raw baby.

Chardonnay seed compound powder can also be used to the amount by reducing lactic acid producing bacteria such as Bacillus acidi lactici in enteron aisle And treat or prevent lactic acidosis.Chardonnay seed compound powder also can be used in the water by improving clostridium in enteron aisle Health that is flat and promoting colon.Clostridial bacteria generates butyrate, this is preferred energy source in mucous membrane of colon.Butyrate protection knot Enteritis and colorectal cancer, and the normal development of colon epithelial cell is important.Shen, J.et al., Applied And Environmental Microbiology, vol.72:5232-5238 (2006).

Chardonnay seed compound powder also can be used in reducing the level of Bifidobacterium in enteron aisle.However, if reducing The level of Bifidobacterium is undesirable, and when another treatment benefit for giving Chardonnay seed meal is desired, then contain The Probiotic supplement of one or more bifidobacterium species can give the subject and improve in subject's enteron aisle The level of bifidobacterium species.The example that the bifidobacterium species in Probiotic supplement can be given includes that Bifidobacterium is double Discrimination bacillus (Bifidobacterium bifidum), bifidobacterium breve (Bifidobacterium breve) and long bifid Bacillus (Bifidobacterium longum).The Probiotic supplement can include other bacteria cultures, for example, it is a kind of or A variety of lactobacillus acidophilus (Lactobacillus acidophilus), lactobacillus plantarum (Lactobacillus Plantarum), saliva Bacillus acidi lactici (Lactobacillus salivarious), Lactobacillus casei (Lactobacillus Casei), secondary Lactobacillus casei (Lactobacillus paracasei), Lactobacillus rhamnosus (Lactobacillus ) and streptococcus thermophilus (Streptococcus thermophilus) rhamnosus.

In one embodiment, the subject, which is confirmed as having, belongs to bacteroid, Ruminococcus or Prevost The microorganism parting of bacterium.In one embodiment, the subject has bacteroid microorganism parting.In an embodiment In, the subject has Ruminococcus microorganism parting.In one embodiment, the subject has melaninogenicus Microorganism parting.

4.5.The therapeutical uses of Chardonnay seed extract composition

According to the present invention, composition of the invention includes Chardonnay seed extract composition, gives subject, preferably Human experimenter, for each therapeutical uses described in Section 4.4.Chardonnay seed extract has the Chardonnay seed The similar biological effect of powder (data are not shown).In order to realize comparable to the benefit for using a certain amount of Chardonnay seed meal to obtain, The dosage of Chardonnay seed extract to be administered should be to provide the 2-5 times of catechin level of the Chardonnay seed meal amount Amount.For obtain daily consumption required for Chardonnay seed meal same benefits with specified rate Chardonnay seed extract it is specific Amount, can easily be determined by those skilled in the art.

5.Embodiment 1: Chardonnay, Sauvignon Blanc (SAUVIGNON BLANC) and White Riesling (WHITE RIESLING) produce The comparison of product health benefits

5.1.Materials & Methods

5.1.1.Hamster and diet

Male golden Syria hamster (~80g, LVG strain, Charles River) is tamed, and in experimental diet Water and 5001 rodent diets (LabDiet, PMI International are arbitrarily given before starting；Albumen, 239g/kg； Fat, 50g/kg；Non-nitrogen containing substance 487g/kg；Crude fibre, 51g/kg；Ash content, 70g/kg；Energy, 17MJ/kg；With for tieing up Hold the sufficient amount minerals and vitamins of health) up to 1 week.Hamster weighs and is randomly divided into 2 groups, every group of 15 hamsters, And feeding contains the Chardonnay of 10wt% (by weight), hundred patchwork vestment worn by a Buddhist monk of solution or hila grape seed powder or grape skin powder or control at random The food rich in fat of (diet) is up to 4 week.The grape growth of the powder is produced in the coastal mountain valley in northern California.The combination of the powder Object is as shown in Figure 1.Diet is configured to 18% protein energy, 43% carbohydrate energy, and 39% adipose energy (is wherein supplemented with 0.1% cholesterol) (Fig. 2) GenOil, refer to a kind of commercial glucose seed oil from unspecified grape variety.Weight is weekly Record and the intake of food monitors weekly twice.The research is by animal care and uses the committee (Animal Care and Use Committee) (Western Regional Research Center, USDA, Albany, CA) ratifies.

5.1.2.Blood plasma and tissue sampling

It hamster fasting 12 hours, is anaesthetized with isoflurane (Phoenix pharmacopeia (Phoenix Pharmaceutical)).With The syringe rinsed in advance with EDTA potassium solution (15%wt:v) collects blood and at 4 DEG C by cardiac puncture with 2000 × g Separated plasma after centrifugation 30 minutes.Liver, weighing are collected, and is frozen in liquid nitrogen immediately for analyzing.

5.1.3.Blood plasma biomarker analysis

Cholesterol in plasma lipoprotein is measured (German et as described previously by size exclusion chromatography Al, 1996.Nutr Res.1996；16:1239-49).Plasma triglyceride, total cholesterol, free cholesterol and glucose are logical It crosses using Roche Diagnistics/Hitachi 914 clinical analysers (Roche Diagnostics/Hitachi with assay kit 914Clinical Analyzer) (Roche Diagnostics and Wako Chemicals) enzyme colorimetric analysis carry out Measurement.The adiponectin (B-bridge International) of fasting hamster and the plasma concentration of insulin (Mercodia) use Foregoing mouse adiponectin and hypersensitive rat insulin immunoassay kit be measured (Hung et al, 2009, J.Diabetes 1:194-206).Blood sugar concentration in fasting hamster uses OneTouch Ultrameter (LifeScan) In It is measured in tail vein sample.

5.1.4.Liver lipid analysis

Freeze-drying grinds liver sample using accelerated solvent extractor agent (Dionex) at 100 DEG C；Under 13.8MPa with 75/25 oneself Alkane/2- propyl alcohol extracts.The sample extraction object is on 914 clinical analysers of Roche Diagnistics/Hitachi (Roche Diagnostics) It analyzes and uses above-mentioned kit measurement liver triglycerides, total cholesterol and free cholesterol.

5.1.5.Fecal bile acid and sterol analysis

Excrement is collected for three days on end immediately before the hamster slaughter, and is lyophilized, and is ground and is stored at -20 DEG C.Bile Acid and sterol pass through HPLC and are measured (Hong et al, 2007, J Agric Food Chem.55:9750- as previously described 7)。

5.1.6.Statistical analysis

All data are represented as average value ± SE.Difference between control and different diet groups passes through double tail student t inspections (2-tailed Student's t test) is tested to be determined.When the variance of each group is not equal, the significance of difference is examined using Webster (Welch's test) is tested to be determined.It calculates Pearson correlation coefficient and studies total plasma cholesterol, Plasma adiponectin is dense Relationship (JMP7 statistics program, the SAS software study institute (SAS of degree, liver cholesterol and triglyceride concentration and liver gene expression Institute)).Conspicuousness is defined as P < 0.05.

5.2.As a result

Compared to the animal of the other diet of feeding, the weight of animals for feeding Chardonnay seed meal significantly reduces (Fig. 3-4). The animal of feeding Chardonnay seed meal diet just has the average weight of about 97g after 4 week.The animal 4 of fed control diet With the average weight of about 110g after a week.

Although the Chardonnay seed treated powder the weight of animals is lower than control-animal, the Chardonnay seed treated powder is dynamic Object eats much (Fig. 5), either according to volume (Fig. 6) or heat (Fig. 7).

The animal of Chardonnay seed meal diet described in feeding shows VLDL (66%) and LDL (50%) cholesterol most It is big to reduce (Fig. 8).Blood glucose shows slightly to reduce (Fig. 9).

Chardonnay seed meal reduces liver weight and epididymal adipose (EA) weight is respectively 30% and 20% (Figure 10).

These statistics indicate that, Chardonnay seed meal obviously protrudes in the grape product tested.The performance of Chardonnay skin powder Similar trend out, but benefit does not have Chardonnay seed meal big like that.

6.Embodiment 2: Chardonnay, Sauvignon Blanc (SAUVIGNON BLANC) and White Riesling (WHITE RIESLING) produce The comparison of the health benefits of product

6.1.Materials & Methods

6.1.1.Hamster and diet

Male golden Syria hamster (~80g, LVG strain, Charles River) is tamed, and in experimental diet Water and 5001 rodent diets (LabDiet, PMI International are given before starting at random；Albumen, 239g/kg； Fat, 50g/kg；Non-nitrogen containing substance, 487g/kg；Crude fibre, 51g/kg；Ash content, 70g/kg；Energy, 17MJ/kg；Be used for Maintain the sufficient amount minerals and vitamins of health) it is up to a week.Hamster weighs and is randomly divided into 10 groups, every group 10 Hamster, and the ethanol extract of seed containing Chardonnay is fed at random, Chardonnay seed methanolic extract, Chardonnay seed ethyl alcohol extracts Residue, Chardonnay seed methanol extract residue, 10% (by weight) Chardonnay seed meal, 10% (by weight) appearance Think of (Sauvignon Blanc) seed meal, 10% (by weight) White Riesling (White Riesling) seed meal, 7% (by weight) Chardonnay seed meal, the high fat diet of 3% (by weight) Chardonnay seed meal or control diet are up to 4 A week.The grape growth of the powder is produced in the coastal mountain valley in northern California.Ethanol extract and extraction residue are by the way that " tea extracts Method " preparation, including the following steps: (1) solvent (ethyl alcohol in 40% distilled water of 1625mL) is added to 325g Chardonnay kind In sub- powder and in 80 DEG C of vibration 2h；(2) mixture of step (1) then passes through 1 filter paper of Whatman and is filtered；(3) then Ethyl alcohol is removed from the filtrate of step (2) on the rotary evaporator；(4) solution of step (3) and the filter cake of step (2) respectively into Row is freezed and is lyophilized and generates Chardonnay seed ethanol extract and Chardonnay seed ethyl alcohol extraction residue.Similar method is used Residue is extracted in production Chardonnay seed methanolic extract and Chardonnay seed methanol.

Diet is configured to 18% energy as albumen, and 43% energy as carbohydrate, 39% as fat Energy (is wherein supplemented with 0.1% cholesterol).Weekly record weight and food intake monitor weekly twice.The research is protected by animal Manage and use the committee (Animal Care and Use Committee) (Western Regional Research Center, USDA, Albany, CA) approval.

6.1.2.Blood plasma and tissue sampling

It hamster fasting 12 hours, is anaesthetized with isoflurane (Phoenix Pharmaceutical).Using in advance with EDTA potassium After the syringe that solution (15%wt:v) rinses is collected blood by cardiac puncture and is centrifuged 30 minutes at 4 DEG C with 2000 × g Separated plasma.Liver, weighing are collected, and is frozen in liquid nitrogen immediately for analyzing.

6.1.3.Blood plasma biomarker analysis

Cholesterol in plasma lipoprotein is measured (German et as described previously by size exclusion chromatography Al, 1996.Nutr Res.1996；16:1239-49).Plasma triglyceride, total cholesterol, free cholesterol and glucose are logical It crosses using Roche Diagnistics/Hitachi 914 clinical analysers (Roche Diagnostics/Hitachi with assay kit 914Clinical Analyzer) (Roche Diagnostics and Wako Chemicals) enzyme colorimetric analysis carry out Measurement.The adiponectin (B-bridge International) of fasting hamster and the plasma concentration of insulin (Mercodia) use Foregoing mouse adiponectin and hypersensitive mouse insulin immunoassay kit be measured (Hung et al, 2009, J.Diabetes 1:194-206).Blood sugar concentration in fasting hamster uses OneTouch Ultrameter (LifeScan) In It is measured in tail vein sample.

6.1.4.Liver lipid analysis

6.1.5.Fecal bile acid and sterol analysis

Excrement is collected for three days on end immediately before the hamster slaughter, and is lyophilized, and is ground and is stored at -20 DEG C.Gallbladder Juice acid and sterol be measured as previously described by HPLC (Hong et al, 2007, J Agric Food Chem.55: 9750-7)。

6.1.6.Statistical analysis

All data are represented as average value ± SE.Difference between control and different diet groups passes through double tail student t inspections (2-tailed Student's t test) is tested to be determined.When the variance of each group is not equal, the significance of difference is examined using Webster (Welch's test) is tested to be determined.It calculates Pearson correlation coefficient and studies total plasma cholesterol, Plasma adiponectin is dense Degree, relationship (JMP7 statistics program, the SAS software study institute (SAS of the expression of liver cholesterol and triglyceride concentration and liver gene Institute)).Conspicuousness is defined as P < 0.05.

6.2.As a result

The Chardonnay seed meal for accounting for the diet 10wt% shows the reproducible result of embodiment 1.Feeding, which has, accounts for drink The weight of animals of the diet of the Chardonnay seed meal of food 10wt% has 35% fat diet compared to control-animal minimum Weight gain.

Chardonnay seed meal shows dosage-response.10%, 7% or 3% Chardonnay seed meal of feeding animal is as its drink A part of food was up to for 4 week.Observe that response gradually increases, this is designated as the difference of weight；Animal eats more, increases The weight added is fewer (Figure 12).

Chardonnay seed extract shows to have a certain impact to weight, but be not directly added into Chardonnay seed meal that Sample is significant.

Chardonnay seed extract and Chardonnay seed extract residue are to cholesterol levels (Figure 13) and LDL/HDL The ratio between (Figure 14) show certain effect, but it is and significant not as good as being directly added into Chardonnay seed meal.Similarly, the rosy clouds Dolly seed extract, which is shown, has a certain effect (Figure 15) organ weight, but and is not so good as to be directly added into Chardonnay seed meal It is significant like that.

Other white seed meals；Such as Sauvignon Blanc (Sauvignon Blanc) or White Riesling (White Riesling) Weight is shown seldom even without difference compared to the control diet.Chardonnay and other four kinds of kinds (mutation) are one by one Compare, and obvious outstanding.

7.Embodiment 3: influence of the Chardonnay seed meal to fat relatively and liver gene expression

7.1.Materials & Methods

7.1.1.Hamster and diet

Male golden Syria hamster (~80g, LVG strain, Charles River) is tamed, and in experimental diet Water and 5001 rodent diets (LabDiet, PMI International are given before starting at random；Albumen, 239g/kg； Fat, 50g/kg；Non-nitrogen containing substance, 487g/kg；Crude fibre, 51g/kg；Ash content, 70g/kg；Energy, 17MJ/kg；Be used for Maintain the sufficient amount minerals and vitamins of health) it is up to a week.Hamster weighs and is randomly divided into 2 groups, and feeds at random It was up to for 4 week containing 10% (by weight) Chardonnay seed meal or control diet.Produce the grape growth Yu Beijia of the powder The coastal mountain valley in state.Diet is configured to 18% energy as albumen, and 43% energy as carbohydrate, 39% as fat Energy (being wherein supplemented with 0.1% cholesterol).Weekly record weight and food intake monitor weekly twice.The research is by animal Nurse and use the committee (Animal Care and Use Committee) (Western Regional Research Center, USDA, Albany, CA) approval.

7.1.2.MRNA analysis

Quantitative PCR (qPCR) is used to measure the hamster for supplementing diet or control diet from Chardonnay seed meal described in feeding Fat and liver sample described in inflammation, cholesterol, the mRNA expression of the selected gene of bile acid and fatty acid pathway.

7.1.3.Statistical analysis

All data are expressed as average value ± SD.Shown average value is the supplement diet of Chardonnay seed meal described in feeding MRNA level in-site is relative to mRNA level in-site in the fat or hepatic tissue of the hamster of feeding control diet in the fat or hepatic tissue of hamster Relative value.

7.2.As a result

Compare Chardonnay seed meal described in feeding supplement diet hamster adipose tissue in gene expression relative to feed The relative gene expression level for eating the gene expression in the adipose tissue of the hamster of control diet is as shown in figure 16.Compare feeding institute State Chardonnay seed meal supplement diet hamster hepatic tissue in gene expression relative to feeding control diet hamster liver The relative gene expression level of gene expression in tissue is as shown in figure 17.

In the hamster of expression Chardonnay seed meal described in feeding supplement diet of liver ACOX1, CYP51 and CYP7al gene It is significant to increase, and simultaneously in the hamster of liver ABCG5 and SCD1 gene expression the Chardonnay seed meal described in feeding supplement diet It is remarkably decreased.

ACOX1 participates in the adjusting of fat oxidation, and CYP51 participates in the adjusting of Biosynthesis of cholesterol, and CYP7al participates in bile The adjusting of acid synthesis, SCD1 participate in Fatty synthesis, and ABCG5 takes part in cholesterol and returns to transport to enteral.Therefore, the result table Bright, the diet of supplement Chardonnay seed meal can reduce the re-absorption of cholesterol and/or bile, lead to the horizontal drop in the liver It is low.The result further demonstrates that the diet for supplementing Chardonnay seed meal can raise fat oxidation by liver gene (ACOX1) and/or by the downward (SCD1) of Fatty synthesis gain is lost weight.

8.Embodiment 4: Chardonnay seed meal and shrimps and crabs seed extract are in contrast to commercial glucose seed extract Health benefits comparison

8.1.Materials & Methods

8.1.1.Hamster and diet

Male golden Syria hamster (~80g, LVG strain, Charles River) is tamed, and in experimental diet Water and 5001 rodent diets (LabDiet, PMI International are given before starting at random；Albumen, 239g/kg； Fat, 50g/kg；Non-nitrogen containing substance, 487g/kg；Crude fibre, 51g/kg；Ash content, 70g/kg；Energy, 17MJ/kg；Be used for Maintain the sufficient amount minerals and vitamins of health) it is up to a week.All grape seed extracts all pass through HPLC method It is characterized and its feeding dosage through overregulating provides 7% (w/w) Chardonnay seed meal identical catechin amount.Hamster weighing And 10 groups are randomly divided into, every group of 8 hamsters, and random feeding includes 7% (by weight) Chardonnay seed meal (1 group),Grape seed extract (2 groups), MegaBP grape seed extract (2 groups),Grape seed extract (2 groups), catechin (about 0.000785g/g diet) (1 group), epicatechin is (about 0.00104g/g diet) (1 group) or (1 group) of control diet was up to for 4 week.Catechin level is used for every kind of grape seed Extract is standardized into the amount of Chardonnay seed meal.Epicatechin and catechin are included in feed diet as these chemical combination The control of object, they show to be responsible for blood pressure and lipid regulation in other researchs.The grape for producing the Chardonnay seed meal is raw It is longer than in northern California seashore mountain valley.Diet include 18% energy as albumen, 43% energy as carbohydrate, 39% Energy as fat (it is supplemented with 0.1% cholesterol).Weekly record weight and food intake monitor weekly twice.The research By animal care and use the committee (Animal Care and Use Committee) (Western Regional Research Center, USDA, Albany, CA) approval.

8.1.2.Blood plasma and tissue sampling

8.1.3.Blood plasma biomarker analysis

8.1.4.Liver lipid analysis

8.1.5.Fecal bile acid and sterol analysis

8.1.6.Statistical analysis

8.2.As a result

The total cholesterol and LDL cholesterol blood plasma level for feeding the animal of Chardonnay seed meal are than feeding supplement commercial glucose The animal of the diet of seed extract significantly reduces (Figure 18-19), but feeding supplementsGrape seed extracts One in the animal groups of the diet of object (L7) is exception.These statistics indicate that, Chardonnay seed meal is better than all, but for dropping Except one of low total cholesterol and the business grape seed extract of LDL cholesterol test.

9.Embodiment 5: influence of the Chardonnay seed meal to fecal microorganism level

9.1.Materials & Methods

9.1.1.Fecal specimens

In the 0th day (control) He, (diet of Chardonnay seed meal supplement, solution hundred patched up the diet of seed meal supplement within 20 days With high-fat control diet) collect embodiment 1 the animal excrement.These excrement are dried and freeze.

9.1.2.RNA is extracted and is quantified

Freezing feces sample is added to 10 times of volumes- ICE (Applied Biosystems, Foster City, CA, USA) in up at least for 24 hours.Total serum IgE uses excrement total serum IgE purification kit (Stool Total RNA Purification Kit) (Norgen Biotek Corp., Canada) prepared according to manufacturers protocol.

The quantity and purity of the isolated RNA is verified by spectrophotometry (A260/A280 ratio).For Every a sample uses 250ng total serum IgE and PrimeScript^TMRT kit (PrimeScript^TM RT reagent kit) (Takara Bio Inc., Shiga, Japan) prepares cDNA according to manufacturers protocol.

Implemented using 7500 real-time PCR system of AB (Applied Biosystems, Foster City, CA, USA) real When PCR enterobacteria 16S rRNA gene expression is quantified.Using SYBR Premix Ex Taq (Takara Bio Inc., Shiga, Japan) implement double amplification.Implemented using the amplification of primer shown in table 1 using following temperature curve: one is followed Ring carries out 30 seconds at 95 DEG C, and carry out 40 circulations below: denaturation carries out 5~10s at 95 DEG C, anneals under optimum temperature (annealating) 5~15s and extend 20s at 72 DEG C.

Table 1

9.2.As a result

Feeding patches up the quantitative real-time PCR knot of the fecal specimens of the hamster of the high fat diet of seed meal containing Chardonnay or solution hundred Fruit shows that the enteric microorganism is adjusted by consuming the powder.It is surveyed in the fecal matter of the hamster of four kinds of diet of feeding The total bacteria levels obtained are as shown in figure 20.The measurement level of bacterial subpopulations is as shown in figures 21-26.

Feeding supplements the hamster fecal specimens of the high fat diet of Chardonnay seed meal compared to high-fat control described in feeding The hamster fecal specimens of diet show Bifidobacterium, and Lactobacillus and the horizontal of Enterobacter significantly reduce, and intestines ball The level that Pseudomonas, fusobacterium IV groups (cluster) bacteriums and bacteroides fragilis belong to dramatically increases.

Feeding supplement solution hundred patches up the hamster fecal specimens of the high fat diet of seed meal compared to high-fat control described in feeding The hamster fecal specimens of diet show the significant decrease of enterobacteria level, and enterococcus spp and bacteroides fragilis group's level significantly increase Add.

10.Specific embodiment and document introduce

All publications quoted in the application, patent, patent application and other documents are all complete with it for all purposes Text is incorporated herein by reference, and degree is each referred to such as each single publication, patent, patent application and other documents It is incorporated herein by reference for all purposes out.

Although various specific embodiments have had been illustrated and described, it is understood that, various change can It enough makes without departing from the spirit and scope of the present invention.

Claims

1. a kind of method for improving lipid-metabolism in mammal, including given to the mammal and effectively improve lipid-metabolism Amount Chardonnay seed products.